Date of Graduation

Summer 2018

Degree

Master of Science in Chemistry

Department

Chemistry

Committee Chair

Reza Sedaghat-Herati

Keywords

Chitosan, Ammonium, Phosphonium, mPEG, Gene Therapy

Subject Categories

Organic Chemistry

Abstract

Chitosan is examined as a non-viral vector capable of efficient gene delivery due to its favorable properties such as biodegradability, biocompatibility, and is non-toxic to mammalian cells. Cell modifications and vector permeability are enhanced in non-viral vectors that incorporate electrostatic interactions. This work synthesizes cationic (N+, P+) chitosan derivatives, to enhance electrostatic interactions towards nucleotides, using amide coupling agents EDC and HOBt. The final chitosan derivatives will bear cationic functional groups (N+, P+) with various alkyl groups (Me, Et, Pr, Ph) to examine their affinities to nucleotides and antifungal properties. mPEG grafted cationic chitosan derivatives were also synthesized to examine enhanced cell permeability. 1H NMR and FT-IR analysis are implemented to observe coupling of cationic ligands to chitosan and examine electron withdrawing effects of changing cationic groups. Turbidity studies were conducted to test chitosan derivatives for pH-dependent solubility. Changes in chitosans stability through loss of intramolecular interactions after ligand coupling was analyzed using TGA-DTG. CD and agarose gel electrophoreses were used to observe cationic chitosan derivatives affinity to nucleotides. Fluorescence Microscopy and Yeast Growth Assays examined anti-fungal properties of cationic derivatives. This work aims to investigate ammonium and phosphonium chitosan derivatives as a viable gene therapy candidate capable of enhanced affinity toward nucleotides.

Copyright

© Quinton Kirk Wyatt

Open Access

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